The goal of this application is to develop a longitudinal cohort study of the short- and long-term health outcomes among individuals who underwent hormonal and/or surgical gender reassignment interventions. Members of the transgender community and health care providers caring for transgender individuals express concerns about mental and physical health problems in this population; however longitudinal studies of transgender populations in the US have not been conducted. This project includes two distinct phases. The first phase is an electronic medical record (EMR) based study evaluating a cohort of 5462 transgender individuals, whose care is covered by the Veterans Administration (nationally) or by Kaiser Permanente (in Georgia and in Northern California). We will compare incidence, prevalence and mortality estimates in the full cohort and in the female-to-male (FTM) and male-to-female (MTF) sub-cohorts to the corresponding measures in the age- and health plan-matched samples of male and female enrollees. We will also perform within-cohort analyses to compare health outcomes across categories of transgender participants (e.g., MTF versus FTM or treatment with hormones versus hormones + surgery). The second phase (Aim 3) of the proposed project will describe facilitators of and barriers to research enrollment, and identify points of influence that would aid recruitment of transgender individuals into future observational studies and intervention trials. This aim will be achieved through Focus Group Discussions (FGDs), and the resulting information will be analyzed using qualitative methods. FGDs will aim to evaluate three central issues: 1) barriers to enrollment in research, 2) facilitators of research participation, and 3) recommendations for recruitment into future studies. The proposed project will be carried out by a multidisciplinary team that includes experts in epidemiology of chronic and sexually transmitted diseases, mental disorders, and sexual minority health issues. All of the project activities will be implemented in consultation wih the study liaisons who will serve as advocates for the transgender community. The proposed study will likely be the largest cohort of transgender individuals available to date, and the first study of its kind conducted in the United States. Another distinguishing feature of this project is that it will lay foundation for future full-scale studies that will use nationwide data sources.